| First Author | Wang H | Year | 2018 |
| Journal | Carcinogenesis | Volume | 39 |
| Issue | 2 | Pages | 158-169 |
| PubMed ID | 29121168 | Mgi Jnum | J:257858 |
| Mgi Id | MGI:6119232 | Doi | 10.1093/carcin/bgx128 |
| Citation | Wang H, et al. (2018) delta-Tocopherol inhibits the development of prostate adenocarcinoma in prostate specific Pten-/- mice. Carcinogenesis 39(2):158-169 |
| abstractText | The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human cancers. Our previous studies demonstrated that delta-tocopherol (delta-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibition of proliferation and induction of apoptosis. Herein, we investigated whether delta-T inhibits the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice in which the activation of AKT is the major driving force for tumorigenesis. By feeding Ptenp-/- mice with AIN93M or 0.2% delta-T supplemented diet starting at the age of 6 or 12 weeks, we found that delta-T treatment reduced prostate adenocarcinoma multiplicity at the age of 40 weeks by 53.3 and 42.7%, respectively. Immunohistochemical (IHC) analysis demonstrated that the phosphorylation of AKT (T308) was reduced in the prostate of the mice administered the delta-T diet. Consistently, proliferation was reduced and apoptosis was increased in prostate lesions of mice on the delta-T diet. Oxidative stress, as determined by IHC staining of 8-OH-dG, was not altered during prostate tumorigenesis, nor was it affected by administration of delta-T. In contrast, alpha-tocopherol (alpha-T) at 0.2% in the diet did not affect prostate adenocarcinoma multiplicity in the Ptenp-/- mice. This finding is consistent with data from our previous study that delta-T, but not alpha-T, inhibits the activation of AKT and the growth of prostate cancer cells. Together, these results demonstrate that delta-T inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, mainly through inhibition of AKT activation. |
